Born Allan See in Mount Kisco, New York, he grew up in Pleasantville and studied acting at Ithaca College, graduating in 1952. His father, a gas station attendant, was a Chippewa (Ojibwa) Indian. After serving in the Air Force, he moved to New York City and worked at Radio City Music Hall while looking for acting work. At about this time he changed his name, drawing "Gavin" from a cerebral palsy victim in a TV drama, and "MacLeod" from his Ithaca drama coach, Beatrice MacLeod.

His first movie appearance was in I Want To Live!, a 1958 prison drama starring the late Susan Hayward who won an Oscar for her performance. He also appeared as the villain on TV shows of the late 1950s and early 1960s. His first regular TV role came in 1962 as Joseph "Happy" Haines on McHale's Navy.

MacLeod's role as "Murray Slaughter" on The Mary Tyler Moore Show won him lasting fame, and two Golden Globe nominations, followed by another three nominations for his Love Boat work.

Along with his wife Patti, an evangelical Christian, he wrote about struggles with divorce and alcoholism in Back On Course: The Remarkable Story of a Divorce That Ended in Remarriage. For a brief time the MacLeods hosted a show on Trinity Broadcasting Network with the same name.